Caspases are a family of cysteine protease enzymes that are key mediators in the signaling pathways for apoptosis and cell disassembly. The utility of caspase inhibitors to treat a variety of mammalian disease states associated with an increase in cellular apoptosis has been demonstrated using peptidic caspase inhibitors. These inhibitors are useful for reducing infarct size and inhibiting cardiomyocyte apoptosis after myocardial infarction, reducing lesion volume and neurological deficit resulting from stroke, reducing post-traumatic apoptosis and neurological deficit in traumatic brain injury, treating fulminant liver destruction, and improving survival after endotoxic shock.
The use of prodrugs imparts desired characteristics such as increased bioavailability or increased site-specificity for known drugs. Accordingly, there is a need for prodrugs of caspase inhibitors.